Therapeutics for the Muscular Dystrophies
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Mission
 Increase the longevity and quality of life of patients with
muscular dystrophy
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Lead Drug Candidate – LAM-111
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Delivered systemically to MDC1A and DMD mouse models
Excellent efficacy with no toxicity
Human LAM-111 in human MDC1A and DMD cells
Human LAM-111 in mouse MDC1A and DMD muscle cells
Stable and scalable human LAM-111 manufacturing
process
 Under evaluation for treatment of dystroglycanopathy
and dysferlinopathy
Ashley
Human LAM-111
No LAM-111
SAM
Adelina
Merosin Deficient (MDC1A)
mice have a reduced lifespan
and normally live between 615 weeks of age, so 1 year is
a very significant milestone
Picture provided by Prothelia
collaborator Dr. Dean
Burkin, University of
Nevada, Reno
Merosin Deficient (MDC1A) mouse treated with laminin-111
(10mg LAM-111/kg/week starting at 10 days of age)
Drug manufacture
Preclinical models
Animal testing
Natural history
Clinical testing
Patient identification
and accrual
Project coordination
Investment
Industry
Science
Investment
Drug
Development
Program
Maia
Development
incentives
Government
Advocacy
Patient referral
Funding support
Trial promotion
Regulatory guidance
Investment
Rare Disease Program
(HTS etc)
Aubrey
Philip
* Data from Pharma drugs developed entirely in-house
$400M in
opportunity costs
All failed Drugs
$1B
Pierce
Preclinical
Development 42%
true costs
Clinical
Development 58%
true costs
Only 1 in 13
Candidates Succeed
3 in 5 Phase III Trials
Succeed
Adams CP, Brantner VV (2010) “Spending on New Drug Development” Health Econ. 19: 130–141 (2010)
Jake
Phase I: About $15K/person
Phase II: About $19K/person
Phase III: About $26K/person
What the non-profit and government
communities have done (funded):
• Funding the “Valley of Death”
• Developing International Patient Registries
• Developing Clinical Research Networks
• Developing and Validating Clinical Endpoints
• Developing Natural History to accurately
power studies
•Standards of Care
*LifeSciences World 10/13/2006
Areas of improvement:
• We need biomarkers to decrease testing time
• We need novel trial designs to reduce costs
and time
• We need centralized IRBs
• We need electronic medical records
• We need clinical data standards
• We need harmonization between the FDA
and EMEA
–
Brad Hodges, PhD
Chairman, SMAB; CSO, Prothelia, Inc.
–
Dean Burkin, PhD
Lead Investigator; Director, Nevada Transgenic Center
for Biomedical Research Excellence, Associate
Professor, University of Nevada School of Medicine
–
Ed Connor, MD
Director, Office of Investigational Therapeutics at
Children's National Medical Center and Professor of
Pediatrics at George Washington University School of
Medicine and Health Sciences
–
Eric Hoffman, PhD
Chairman, Department of Integrative Systems Biology,
George Washington University School of Medicine and
Health Sciences and Director, Research Center for
Genetic Medicine at Children's National Medical Center
–
George Vella, PhD
Director of Research and Strategic Planning,
Charley’s Fund
–
John M McCall, PhD
President, PharMac LLC
–
Markus A Ruegg, PhD
Professor of Neurobiology, Biozentrum
University of Basel
–
Steve D Hauschka, PhD
Professor of Biochemistry, University of Washington
Kyra
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Scientists/Clinicians
–
Jim Collins, MD, PhD
Assistant Professor of Pediatric Neurology,
University of Cincinnati College of Medicine,
Pediatric Neurologist, Cincinnati Children’s Hospital
Medical Center
–
Jim Dowling, MD, PhD
Assistant Professor, Division of Pediatric Neurology,
Pediatric Neurologist, University of Michigan
–
Kathy Mathews, MD
Director, Division of Pediatric Neurology, Development
and Behavior Professor, Departments of Pediatrics and
Neurology, University of Iowa Carver College of
Medicine, University of Iowa Children’s Hospital
–
Xiao Xiao, PhD
Fred Eshelman Distinguished Professor of Gene
Therapy, University of North Carolina, UNC Eshelman
School of Pharmacy
–
Brenda Wong, MD
Associate Professor of Clinical Pediatrics and Neurology,
Director, Pediatric Neuromuscular Program and MDA
Clinic, Cincinnati Children’s Hospital Medical Center
–
Robert Griggs, MD, FAAN
Professor of Neurology, Medicine, Pediatrics Pathology and
Laboratory Medicine, University of Rochester School of
Medicine, Chair, Muscle Study Group Executive Committee
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Patient Advocacy Groups
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Cure CMD (Congenital Muscular Dystrophy)
Struggle Against Muscular Dystrophy (SAM), Ireland
Muscular Dystrophy Association (MDA)
Parent Project Muscular Dystrophy (PPMDP)
Charley’s Fund, Inc.
Government Organizations
– National Institute of Health (NIH) – financial support (3 grants)
– Treat-NMD (Neuromuscular Disease), European Union
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